This invention relates to prostaglandin derivatives and to processes for preparing them.
The prostaglandins are a well-known group of organic compounds, including for example Prostaglandin F.sub.2.alpha. (PGF.sub.2.alpha.) represented by formula I.
The prostaglandins are related to prostanoic acid which has the structure and atom numbering of formula II.
For background on prostaglandins, see for example Bergstrom et al., Pharmacol. Rev. 20, 1 (1968). For nomenclature of the prostaglandins, see N. A. Nelson, J. Medic. Chem. 17, 911 (1974). In the literature, PGF.sub.2.alpha. may be variously indexed, for example as a derivative of "prosta-5,13-dien-1-oic acid" or "5-heptenoic acid". With respect to "R" and "S" usage, as for the stereochemistry of substituent groups at C-15 herein, see R. S. Cahn, J. Chem. Ed. 41, 116 (1964).
As drawn herein the formulas represent a particular optically active isomer having the same absolute configuration as PGE.sub.1 obtained from mammalian tissues.
In the formulas, broken line attachments to the cyclopentane ring or side chain indicate substituents in alpha configuration, i.e. below the plane of the ring or side chain. Heavy solid line attachments indicate substituents in beta configuration, i.e. above the plane.
Included in the background of chemical literature and patents are the following: K. Green et al., J. Lipid Res. 5, 117 (1969), PGE.sub.3 and PGF.sub.3.alpha., methyl esters; B. Samuelsson, U.S. Pat. No. 3,657,316, 19-hydroxy-PGE.sub.1 ; P. L. Taylor et al., Nature 250, 665 (1974) and FEBS Letters 57, 22 (1975), 19-hydroxy-PGE's and -PGF's; W. Marscheck et al., U.S. Pat. No. 3,878,046, 11-deoxy-19-hydroxy-PGE.sub.2 ; C. J. Sih et al., J. Am. Chem. Soc. 91, 3685 (1969), 19-oxo-PGE.sub.2 and -13,14-dihydro-PGE.sub.1 ; J. C. Sih, Prostaglandins 13, 831 (1977), (19R)-19-hydroxy-PGE.sub.1, -PGE.sub.2, -PGF.sub.1.alpha., and -PGF.sub.2.alpha. ; Brit. Pat. Spec. No. 1,388,443, Derwent Farmdoc Abstract No. 00520U, reduction of 9,19-diketoprostanoic acids; A. F. Marx et al., U.S. Pat. No. 4,054,595, 18- and 19-hydroxy-prostaglandins; J. E. Pike, U.S. Pat. No. 3,922,297, 19-methyl-prostaglandins; R. K. Beerthuis et al., Rec. Trav. Chim. Pays. Bas 90, 943 (1971), cis-.DELTA..sup.18 -PGE.sub.1 ; K. G. Untch et al., J. Am. Chem. Soc. 100, 6211 (1978), dl-19-hydroxy-PGE.sub.1 and dl-13-cis-15-epi-19-hydroxy-PGE.sub.1 ; German Offenleg. 2,505,519 (Derwent Farmdoc Abstract No. 56027W) or Chem. Abs. 84, 43441w, 20-hydroxy-PGE.sub.2 or -PGF.sub.2.alpha..
Subsequent to this invention there appeared U.S. Pat. No. 4,127,612 to H. C. Kluender et al. for 2-decarboxy-2-hydroxymethyl-19-hydroxy-PGE.sub.1 and 19-hydroxy PGE.sub.1 carbinol analogues.